ReviewLiver involvement in hereditary hemorrhagic telangiectasia (HHT)
Introduction
Liver vascular malformations can come to the attention of a hepatologist through their fortuitous discovery during the performance of an imaging study or through the presence of symptoms suggestive of liver disease. Liver vascular malformations are being discovered fortuitously more frequently with the increasing performance of sensitive imaging techniques. In adults, the most common cause of diffuse vascular malformations in the liver is hereditary hemorrhagic telangiectasia (HHT). On the other hand, symptoms related to liver involvement by HHT such as abdominal pain, cholestasis, cholangitis, ascites, variceal hemorrhage and/or encephalopathy can also lead to hepatological consultation. Therefore, the hepatologist needs to recognize the variable presentations, diagnosis and treatment of liver involvement in HHT.
Section snippets
Background on HHT
HHT or Rendu–Osler–Weber disease is a genetic disease with an autosomal dominant inheritance pattern, characterized by widespread telangiectases that can involve the skin, mucous membranes, lung, brain, the gastrointestinal tract and/or liver. It has an estimated prevalence of 1–2 cases per 10,000.
The telangiectasia is the characteristic lesion of HHT. It arises from a dilated post capillary venule that enlarges and fuses with an arteriole bypassing the capillary system and resulting in an
Liver involvement by HHT
Liver involvement by HHT is characterized by widespread diffuse liver vascular malformations (VMs) that, given the dual blood supply to the liver, give rise to three types of shunting: arteriovenous (hepatic artery to hepatic vein), arterioportal (hepatic artery to portal vein), and portovenous (portal vein to hepatic vein). Anatomically, liver vascular abnormalities vary in size. Although small macroscopic VMs can be seen radiographically, microscopic abnormal direct communications between
Epidemiology
The prevalence of hepatic involvement in HHT had been estimated to be between 8% and 31% in retrospective studies [11], [12] but in more recent large prospective studies, in which Doppler ultrasound or multi-slice computed tomography (CT) has been performed systematically in HHT-affected subjects, the prevalence is higher ranging between 41% [13] and 78% [14], [15]. However, most patients are asymptomatic.
Symptomatic liver involvement is quite rare as demonstrated by a search of the English
Clinical features
Symptoms occur in about 8% of the patients with HHT and liver VMs demonstrated on imaging studies [13], [14].
Symptoms appear around the age of 30 and occur predominantly in females. The three most common initial clinical presentations and their distinguishing characteristics are shown in Table 2. Importantly, these presentations may occur concurrently or successively and may have spontaneous exacerbations and remissions.
Porto-systemic encephalopathy
Less commonly, patients may also develop porto-systemic encephalopathy (PSE), condition that has been reported in 4 cases [6], [59], [60], two of which had [59] or later developed [6] symptoms of heart failure. In fact, although in our original series no patient had presented with PSE [16], it has since developed in two patients in the heart failure group.
Abdominal angina
Another even less common presentation is that of abdominal angina secondary to mesenteric arterial “steal” syndrome that has been reported as
Pathophysiology of clinical presentations
As shown in Fig. 1, the different clinical presentations of liver involvement by HHT are mostly due to vascular shunting.
The most frequent presentation, high output heart failure, is the result of shunting of blood from the hepatic artery and/or the portal vein into the systemic circulation producing a hyperdynamic circulatory state that eventually leads to a high output type of heart failure.
The development of portal hypertension has two possible mechanisms, the most obvious being shunting of
Diagnosis
In a patient without known HHT, the diagnosis of liver involvement by HHT requires a high degree of suspicion. A personal and/or family history of epistaxis, telangiectases (cutaneous or mucosal), heart failure, cerebrovascular accident, abscesses or liver disease in a patient with “cirrhosis”, cholangitis or liver test abnormalities should raise the suspicion of HHT and liver VMs. In a patient with known HHT, the presence of shortness of breath and/or edema in the absence of pulmonary AVMs or
Treatment
No treatment is recommended for patients with asymptomatic liver involvement by HHT. In patients with symptomatic liver involvement, treatment can be divided into symptomatic treatment of the specific complications, treatment aimed at reducing shunting and liver transplantation.
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